Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD14 |
|---|
| MTBC0 PGAP re-annotation | long-chain fatty acid--CoA ligase |
|---|
| Revised (this work) | Long-chain fatty acid--CoA ligase. Pfam: AMP-binding (PF00501.35), AMP-binding_C (PF13193.13). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53406
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | Long-chain-fatty-acid--CoA ligase FadD13 |
|---|
| EC (curated) |
EC 6.2.1.3
|
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|
| Preferred name | fadD14 |
|---|
| eggNOG description | PFAM AMP-dependent synthetase and ligase |
|---|
| Orthologous group | COG0318 |
|---|
| KEGG orthology |
K00666
|
|---|
| Gene Ontology (17) |
GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005777, GO:0042579, GO:0043226, GO:0043227, GO:0043229 +5 more
|
|---|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are
computed annotations, not manual curation; cross-check against the primary literature
before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
pseudogene candidate
| pN/pS |
0.372 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
7 synonymous, 7 missense, 1 nonsense, 0 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
1.66% of strains
(2417) · clonal
|
|---|
pN/pS from segregating SNPs (singletons removed) normalised by possible sites.
Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene).
A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic
variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A
clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a
convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
AMP-binding | PF00501.35 |
4.7e-87 | 23–398 |
AMP-binding enzyme |
AMP-binding_C | PF13193.13 |
1.9e-18 | 446–521 |
AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1059 hyp |
hypothetical protein |
793 |
793 ctx |
neighborhood:788 |
Rv1060 hyp |
hypothetical protein |
775 |
774 ctx |
neighborhood:738 |
Rv1057 hyp |
hypothetical protein |
774 |
774 ctx |
neighborhood:768 |
Rv1062 hyp |
hypothetical protein |
716 |
716 ctx |
neighborhood:712 |
Rv1061 hyp |
hypothetical protein |
714 |
714 ctx |
neighborhood:712 |
Rv0719 rplF |
50S ribosomal protein L6 |
695 |
695 |
experimental:402 database:510 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase |
705 |
680 |
|
Rv1527c pks5 |
polyketide synthase |
704 |
679 |
|
Rv2048c pks12 |
polyketide synthase |
704 |
679 |
|
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC |
704 |
679 |
|
Rv2940c mas |
multifunctional mycocerosic acid synthase |
704 |
679 |
|
Rv3800c pks13 |
polyketide synthase |
672 |
635 |
|
Rv2946c pks1 |
polyketide synthase |
663 |
631 |
|
Rv1661 pks7 |
polyketide synthase |
630 |
609 |
|
Rv1181 pks4 |
polyketide beta-ketoacyl synthase |
629 |
608 |
|
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression,
experimental, database, text-mining) into a 0–1000 score. The ctx
badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion,
phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an
unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not
depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with
the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: fatty-acid--CoA ligase FadD14
- MTBC0 PGAP product: long-chain fatty acid--CoA ligase
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=5e-87), AMP-binding_C PF13193.13 (E=2e-18)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024),
An imputed ancestral reference genome for the MTBC,
doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215574.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-binding_C (PF13193.13)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0318
- Curated reference: UniProt
O53406
(TrEMBL, unreviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of
145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
78 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001138|Rv1058|fadD14
MYGTMQDFPLTITAIMRHGCGVHGRRTVTTATGEGYRHSSYRDVGQRAGQLANALRRLGVTGDQRVATFMWNNTEHLVTYFAVPSMGAVLHTLNIRLFPEQIAYVTNEAEDRVILVDLSLARLLAPVLPKLDTVHTVIAVGEGDTTPLREAGKTVLRFAELIDAESPDFGWPQIDENSAAAMCYTSGTTGNPKGVVYSHRSSFLHTMAACTTNGIGVGSSDKVLPIVPMFHANGWGLPYAALMAGADLVLPDRHLDARSLIHMVETLKPTLAGAVPTIWNDVMHYLEKDPDHDMSSLRLVACGGSAVPESLMRTFEDKHDVQIRQLWGMTETSPLATMAWPPPGTPDDQHWAFRITQGQPVCGVETRIVDDDGQVLPNDGNAVGEVEVRGPWIAGSYYGGRDESKFDSGWLRTGDVGRIDEQGFITLTDRAKDVIKSGGEWISSVELENCLIAHPDVLEAAVVGVPDERWQERPLAVVVVREGATVSAGDLRAFLADKVVRWWLPERWAFVDEIPRTSVGKYDKKAIRSRYAEGAYQITEVHT
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